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, Volume 14, Issue 5–6, pp 643–648 | Cite as

Desensitization of rat mast cells: studies of some effects of anti-allergic drugs

  • V. Holford-Strevens
Histamine and Kinins

Abstract

Peritoneal mast cells from rats immunized with dinitrophenylated ovalbumin (DNP-OA) or normal cells passively sensitized with mouse anti-DNP-OA were incubatedin vitro with DNP-bovine serum albumin in the absence of Ca++. This procedure induced desensitization of the cells, such that histamine release was inhibited on subsequent challenge with OA, in the presence of Ca++. The phenomenon of desensitization is supposed to involve early stages in the histamine release process and, thus, two anti-allergic drugs, disodium cromoglycate and doxantrazole, which inhibit an early event(s), were added with the Ca++-free antigen to investigate whether they had any effect on desensitization. The inhibition of final histamine release caused by each drug and that due to desensitization were approximately additive. It was concluded that the drugs did not influence desensitization of rat mast cells. Thus, their activity was consistent with an effect on an event in the histamine release process, occurring after the generation of the activated stage believed to be responsible for desensitization.

Keywords

Albumin Serum Albumin Mast Cell Histamine Normal Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. [1]
    J.C. Foreman andL.G. Garland,Desensitization in the process of histamine secretion induced by antigen and dextran. J. Physiol., Lond.239, 381–391 (1974).Google Scholar
  2. [2]
    S. Norn andP. Stahl Skov,Anaphylactic hyposensitization of rat mast cells in vitro by antigen. Clin. exp. Immunol.18, 431–437 (1974).Google Scholar
  3. [3]
    L.M. Lichtenstein andA.G. Osler,Studies on the mechanisms of hypersensitivity phenomena. IX. Histamine release from human leukocytes by ragweed pollen antigen. J. exp. Med.120, 507–530 (1964).Google Scholar
  4. [4]
    L.M. Lichtenstein,The immediate allergic response: in vitro separation of antigen activation, decay and histamine release. J. Immunol.107, 1122 (1971).Google Scholar
  5. [5]
    J.C. Foreman, L.G. Garland andJ.L. Mongar,The role of calcium in secretory processes: model studies in mast cells. Symp. Soc. exp. Biol.30, 193–218 (1976).Google Scholar
  6. [6]
    J.C. Foreman andL.G. Garland,Cromoglycate and other anti-allergic drugs: a possible mechanism of action. Br. med. J.i, 820–822 (1976).Google Scholar
  7. [7]
    L.G. Garland andJ.L. Mongar,Differential histamine release by dextran and the ionophore A23187: the actions of inhibitors. Int. Archs Allergy appl. Immun.50, 27–42 (1976).Google Scholar
  8. [8]
    H. Nagai, K. Kelly andA.H. Sehon,The inhibition of histamine release by anti-allergic drugs. Int. Archs Allergy appl. Immun.56, 307–315 (1978).Google Scholar
  9. [9]
    H.G. Johnson andM.K. Bach,Prevention of calcium ionophore induced release of histamine in rat mast cells by disodium cromoglycate. J. Immun.114, 514–516 (1975).Google Scholar
  10. [10]
    W.Y. Lee andA.H. Sehon,Suppression of reaginic antibody formation. I. Induction of hapten specific tolerance. J. Immun.114, 829–836 (1975).Google Scholar
  11. [11]
    C.D. May, M. Lyman, R. Alberto andJ. Cheng,Procedures for immunochemical study of histamine release from leukocytes with small volume of blood. J. Allergy46, 12–20 (1970).Google Scholar
  12. [12]
    E.J. Kusner, B. Dubnick andD.J. Herzig,The inhibition by disodium cromoglycate in vitro of anaphylactically induced histamine release from rat peritoneal mast cells. J. Pharmac. exp. Ther.184, 41–46 (1973).Google Scholar
  13. [13]
    D.S. Thompson andD.P. Evans,Inhibition of immediate hypersensitivity reactions by disodium cromoglycate. Requirements for activity in two laboratory models. Clin. exp. Immunol.13, 537–544 (1973).Google Scholar
  14. [14]
    A.K. Sobotka, M. Dembo, B. Goldstein andL.M. Lichtenstein,Antigen-specific desensitization of human basophils. J. Immun.122, 511–517 (1979).Google Scholar
  15. [15]
    R.P. Siraganian andK.A. Hazard,Mechanisms of mouse mast cell activation and inactivation for histamine release. J. Immun.122, 1719–1725 (1979).Google Scholar
  16. [16]
    W. Kazimierczak andB. Diamant,Mechanisms of histamine release in anaphylactic and anaphylactoid reactions. Prog. Allergy24, 295–365 (1978).Google Scholar
  17. [17]
    F. Hirata andJ. Axelrod,Phospholipid methylation and biological signal transmission. Science209, 1082–1090 (1980).Google Scholar
  18. [18]
    M. Dembo, B. Goldstein, A.K. Sobotka andL.M. Lichtenstein,Degranulation of human basophils: quantitative analysis of histamine release and desensitization, due to a bivalent penicilloyl hapten. J. Immun.123, 1864–1872 (1979).Google Scholar
  19. [19]
    M. Dembo andB. Goldstein,A model of cell activation and desensitization by surface immunoglobulin: the case of histamine release from human basophils. Cell22, 59–67 (1980).Google Scholar
  20. [20]
    D.W. MacGlashan andL.M. Lichtenstein,The transition from specific to nonspecific desensitization in human basophils. J. Immun.127, 2410 (1981).Google Scholar
  21. [21]
    P. Stahl Skov, S. Norn andA. Wiik,Binding of antigen to surface Ig during in vitro hyposensitization of isolated rat mast cells. Allergy34, 43–49 (1979).Google Scholar
  22. [22]
    J.C. Spitzer,Interaction of doxantrazole with calcium ions in solvents of intermediate polarity. Int. Archs Allergy appl. Immun.61, 75–80 (1980).Google Scholar
  23. [23]
    W.A. Taylor, D.H. Francis, D. Sheldon andI.M. Roitt,Anti-allergic actions of disodium cromoglycate and other drugs known to inhibit cyclic 3′, 5′-nucleotide phosphodiesterase. Int. Archs Allergy appl. Immun.47, 175–193 (1974).Google Scholar
  24. [24]
    K. Barrett-Bee andW. Henderson,A comparison of the inhibition of phosphodiesterase activity and allergic histamine release by disodium cromoglycate and compound I.C.I. 74917. Biochem. Soc. Trans.4, 699–701 (1976).Google Scholar
  25. [25]
    T.C. Theoharides, W. Sieghart, P. Greengard andW.W. Douglas,Anti-allergic drug cromolyn may inhibit histamine secretion by regulating phosphorylation of a mast cell protein. Science207, 80–82 (1980).Google Scholar
  26. [26]
    M. Ennis, G. Atkinson andF.L. Pearce,Inhibition of histamine release induced by compound 48/80 and peptide 401 in the presence and absence of calcium. Implications for the mode of action of anti-allergic compounds. Agents and Actions10, 222–228 (1980).Google Scholar
  27. [27]
    M. Ennis, F.L. Pearce andP.M. Weston,Some studies on the release of histamine from mast cells stimulated with polylysine. Br. J. Pharmac.70, 329–334 (1980).Google Scholar
  28. [28]
    R. Gonzalez Alvarez andW. Kazimierczak,New light on the mechanism of action of disodium cromoglycate. Agents and Actions11, 94–96 (1981).Google Scholar

Copyright information

© Birkhäuser Verlag 1984

Authors and Affiliations

  • V. Holford-Strevens
    • 1
  1. 1.Medical Research Council Group for Allergy Research, Department of ImmunologyUniversity of ManitobaWinnipegCanada

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